Abstract
Increasing evidence in recent years has suggested that regulatory B cells (Bregs) are one of the crucial modulators in various inflammatory disease conditions. However, no study to date has investigated the significance of Bregs in modulating osteoclastogenesis. To the best of our knowledge, in the present study, we for the first time examined the anti-osteoclastogenic potential of Bregs under in vitro conditions and observed that Bregs suppress RANKL-induced osteoclastogenesis in a dose-dependent manner. We further elucidated the mechanism behind the observed suppression of osteoclasts differentiation via Bregs. Our results clearly suggested that the observed anti-osteoclastogenic property of Bregs is mediated via the production of IL-10 cytokine. Next, we explored whether Bregs have any role in mediating inflammatory bone loss under post-menopausal osteoporotic conditions in ovx mice. Remarkably, our in vivo data clearly suggest that the frequencies of both CD19+IL-10+ Bregs and CD19+CD1dhiCD5+IL-10+ “B10” Bregs were significantly reduced in case of osteoporotic mice model. Moreover, we also found a significant reduction in serum IL-10 cytokine levels in osteoporotic mice, thereby further supporting our observations. Taken together, the present study for the first time establishes the direct role of regulatory B cells in modulating osteoclastogenesis in vitro. Further, our in vivo data suggest that modulations in the percentage of Bregs population along with its reduced potential to produce IL-10 might further exacerbate the observed bone loss in ovx mice.
Highlights
B cells are classically characterized by their potential to produce and secrete antibodies
Our flow cytometric data indicates that the frequency of total IL-10 producing B cells, i.e., CD19+IL-10+ Regulatory B cells (Bregs) was significantly enhanced by LPS stimulation in a time-dependent manner in comparison to the control group (p < 0.001) (Figures 1B, C)
Various studies demonstrated that the homeostatic balance between anti-inflammatory (Tregs) and inflammatory (Th17) cells is of utmost importance in various diseases including osteoporosis [13, 16, 24]
Summary
B cells are classically characterized by their potential to produce and secrete antibodies They function as antigen-presenting cells (APCs) and secrete several immunomodulatory cytokines. In the presence of toll-like receptor (TLR) ligands, such as lipopolysaccharide (LPS), CpG, and CD40L, the development of Bregs can be optimized [3, 4] These Bregs exhibit the ability to regulate various disease conditions including inflammatory bone loss diseases such as rheumatoid arthritis (RA), collagen-induced arthritis (CIA), etc. Given that IL-10 producing B cells play a crucial role in immune regulation, Tedder et al defined a subset of Bregs named “B10 cells” whose anti-inflammatory potential is only attributable to the production of IL-10 cytokine in various disease models such as cancer, autoimmune diseases, and infectious diseases. Multiple studies in both humans and mice highlighted that Bregs suppress inflammatory reactions via IL-10 cytokine
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